Lymph Node Staging in Perihilar Cholangiocarcinoma: The Key to the Big Picture.

Klatskin tumors have a bad prognosis despite aggressive therapy. The role and extent of lymph node dissection during surgery is a matter of discussion. This retrospective study analyzes our current experience of surgical treatments in the last decade. Patients and Methods: A retrospective single-center analysis of patients (n = 317) who underwent surgical treatment for Klatskin tumors. Univariable and multivariable logistic regression and Cox proportional analysis were performed. The primary endpoint was to investigate the role of lymph node metastasis for patient survival after complete tumor resection. The secondary endpoint was the prediction of lymph node status and long-term survival from preoperatively available parameters. Results: In patients with negative resection margins, a negative lymph node status was the prognosis-determining factor with a 1-, 3-, and 5-year survival rate of 87.7%, 37%, and 26.4% compared with 69.5%, 13.9%, and 9.3% for lymph-node-positive patients, respectively. Multivariable logistic regression for complete resection and negative lymph node status demonstrated only Bismuth type 4 (p = 0.01) and tumor grading (p = 0.002) as independent predictors. In multivariate Cox regression analysis, independent predictors of survival after surgery were the preoperative bilirubin level (p = 0.03), intraoperative transfusion (p = 0.002), and tumor grading (G) (p = 0.001). Conclusion: Lymph node dissection is of utmost importance for adequate staging in patients undergoing surgery for perihilar cholangiocarcinoma. In spite of extensive surgery, long-term survival is clearly associated with the aggressiveness of the disease.

Bridging treatment prior to liver transplantation for hepatocellular carcinoma: radioembolization or transarterial chemoembolization?

BACKGROUND: In hepatocellular carcinoma (HCC) patients, intraarterial therapies are regularly employed as a bridge to liver transplantation to prevent tumor progression during waiting time. Objective of this study was to compare HCC recurrence after liver transplantation following TACE or radioembolization bridging treatment. METHODS: We retrospectively analyzed prospectively collected data on 131 consecutive HCC patients who underwent liver transplantation between January 2007 and December 2017 at our liver transplant center (radioembolization n = 44, TACE n = 87). Multivariable logistic regression and cox proportional hazard regression models were used to evaluate factors associated with tumor recurrence and post-transplant survival. RESULTS: Between groups, patients were comparable with regards to age and gender. In the radioembolization group, Milan criteria for HCC were met significantly less frequently (20.5% vs. 65.5%, p < 0.0001). Patients in the radioembolization group required significantly fewer intraarterial treatments (1 [1-2] vs. 1 [1-7], p = 0.0007). On explant specimen, tumor differentiation, microvascular invasion and tumor necrosis were comparable between the groups. HCC recurrence and overall survival were similar between the groups. Multivariable analysis detected increasing recipient age, male gender, complete tumor necrosis and absence of microvascular invasion being independently associated with decreased odds for HCC recurrence. Increasing model of end-stage liver disease (MELD) score and tumor recurrence were independently associated with increased odds of post-transplant death. CONCLUSIONS: Intraarterial bridging treatment leading to tumor necrosis may not only prevent waitlist drop-out but also facilitate long-term successful liver transplantation in HCC patients. Both radioembolization and TACE represent potent treatment strategies.

Balancing Outcome vs. Urgency in Modern Liver Transplantation.

Background: Current allocation mechanisms for liver transplantation (LT) overemphasize emergency, leading to poorer longtime outcomes. The utility was introduced to recognized outcomes in allocation. Recently, Molinari proposed a predictive outcome model based on recipient data. Aims: The aims of this study were to validate this model and to combine it with the utility to emphasize outcome in allocation. Methods: We retrospectively analyzed 734 patients who were transplanted between January 2010 and December 2019. Points were assigned as in Molinari's model and the score sum was correlated with observed 90-day mortality. The utility was calculated as the product of 1-year survival times 3-month mortality on the waiting list. The weighting of different compounds was introduced, and utility curves were calculated. Model for End-Stage Liver Disease (MELD) scores according to maximal utility were determined. Results: In total, 120 patients (16.3%) had died within 90 days after LT. Higher MELD score, obesity, and hemodialysis prior to LT were confirmed risk factors. Overall survival was 83.8 and 77.4% after 90 days and 12 months, respectively. General utility culminated at MELD scores >35 in the overall population. Emphasizing the outcome shifted the maximal utility to lower MELD scores depending on Molinari scores. Conclusions: Emphasizing outcome, at least in certain recipient risk categories, might improve the longtime outcomes and might be integrated into allocation models.

The rate of cholangiocarcinoma in Caroli Disease A German multicenter study.

BACKGROUND: Caroli Disease (CD) and Caroli Syndrome (CS) are rare disorders presenting with dilation of the intrahepatic bile ducts. CD/CS are associated with cholangiocarcinoma (CCA). However, the true incidence of CCA is still unclear, although it may serve as an indication for surgery. In this paper, we analyzed (I) the incidence of CCA in German centers, (II) reviewed our single center population together with its clinical presentation and (III) performed a thorough literature review. METHODS: 17 large HPB-centers across Germany were contacted and their patients after surgical treatment due to CD/CS with histopathology were included. Medline search for all studies published in English or German literature was performed. Patients who underwent surgery at our department between 2012 and 2020 due to CD or CS were analyzed. RESULTS: In the multicenter study, 79 patients suffered from CD and 119 patients from CS, with a total number of 198 patients. In 14 patients, CCA was found (Overall: 7,1%; CD: 6,3%, CS 7,6%). Between 2012 and 2020, 1661 liver resections were performed at our department. 14 patients underwent surgery due to CD or CS. Histological examination showed synchronous cholangiocarcinoma in one patient. The literature review revealed a CCA-rate of 7,3% in large series, whereas in case reports a rate of 6,8% was found. CONCLUSION: There is risk of malignant transformation and patients with CD might also benefit from resection due to improvement of symptoms. Therefore, resection is strongly advised. As certain patients with CS require transplantation, treatment should not be guided by the relatively low rate of CCA but by the concomitant diseases that come along with hepatic failure.

HTK-N as a new preservation solution for human kidney preservation: Results of a pilot randomized controlled clinical phase II trial in living donor transplantation.

BACKGROUND: HTK-N was developed based on the traditional HTK preservation solution, resulting in stronger protection against reactive oxygen species as well as better tolerance to hypothermia and ischemia. Aim of the present study was to compare HTK-N to HTK in clinical kidney transplantation demonstrating safety and non-inferiority. METHODS: We performed a randomized controlled single blinded clinical phase II trial in patients undergoing living donor kidney transplantation. After retroperitoneoscopic nephrectomy kidneys were either perfused and stored with classical HTK solution or the new HTK-N solution. Primary endpoint was the glomerular filtration rate (eGFR according to CKD EPI) 3 months after transplantation. Secondary endpoints included graft and patient survival beside others. RESULTS: The study included 42 patients, of which 22 were randomized in the HTK-N group and 20 in the HTK group. The primary end point showed a mean eGFR of 55.4 ± 14.0 ml/min/1.73 m2 in the HTK group compared to a GFR of 57.2 ± 16.7 ml/min/m2 in the HTK-N group (P = .72). Regarding secondary endpoints, there were no apparent differences. Posttransplant graft and patient survival was 100%. CONCLUSION: This study is the first clinical application of HTK-N for kidney preservation and demonstrates non-inferiority compared to HTK in the setting of living donor kidney transplantation.

Transcriptomic profiles of human livers undergoing rewarming machine perfusion before transplantation-first insights.

Machine perfusion by controlled oxygenated rewarming (COR) is feasible and safe in clinical application and result in a promising outcome. This study utilizes next-generation sequencing (NGS) to investigate the transcriptome of human liver tissue undergoing COR before liver transplantation. Cold-stored livers were subjected to machine-assisted slow COR for ~120 min before transplantation. Biopsies were taken before (preCOR) and after COR (postCOR) and 1 h after reperfusion (postRep). The samples were sequenced, using RNA-seq to analyze differential transcriptional changes between the different stages and treatments of the grafts. Comparison of differential gene expression preCOR and postCOR demonstrated 10 upregulated genes. postRep 97 and 178 genes were upregulated and 7 and 13 downregulated compared to preCOR and postCOR, respectively. A shift of gene expressions by machine perfusion to the TGF-beta pathway was observed. The present study demonstrates distinct transcriptome profiles associated with machine perfusion by COR and transplantation of human livers. Such data provide a deeper understanding of the molecular mechanisms of machine perfusion technology in human liver transplantation.

Kidney transplantation with allografts from infant donors-Small organs, big value.

BACKGROUND: Although infant organ donors remain a rare source of organs for transplantation, technical challenges have resulted in increased rates of complications and inferior graft function. The aim of the present study was to investigate the outcomes of kidneys procured from juvenile and infant donors. PATIENTS AND METHODS: We evaluated all kidney transplants from deceased donors < 16 years of age performed at our center between 01/2008 and 08/2019. We defined three groups based on quartiles of donor body weight: <13 kg (infant donors), 13-40 kg (juvenile donors), and > 40 kg (standard criteria donors). Clinical characteristics and outcomes were compared between groups. RESULTS: Ninety-two transplants were included in this study. Out of 92 recipients, there were 32 (34.8%) adult and 60 (65.2%) pediatric patients. All groups demonstrated excellent graft function and survival on both short and long-term follow-up. 1-year, 3-year, and 5-year graft survival rates for the standard criteria donor group were 100%, 95.2%, and 88.4%, respectively, compared with 95.8% for infant and 95% for juvenile donors at all times (P = .79). eGFR at 5 years was 98.9 ± 5.5, 74.1 ± 6.2, and 81.6 ± 6.9 mL/min/1.73 m2 for infant, juvenile, and standard criteria donors, respectively (P < .01). CONCLUSION: Infant donor allografts can be transplanted with excellent long-term outcomes in both pediatric and adult recipients. Implanting them as single allografts onto pediatric candidates allows for the transplantation of two patients. As such, pediatric recipients should be prioritized for these donor organs.

Long-term Outcomes After Controlled Oxygenated Rewarming of Human Livers Before Transplantation.

Controlled oxygenated rewarming (COR) has been shown to be a feasible and safe method in clinical practice and to reduce peak serum transaminases after liver transplantation. This study aimed to demonstrate further clinical experience of this method of now 18 clinical liver transplantations utilizing COR and demonstrate the long-term results. METHODS: In this extended series of 18 patients, cold-stored livers were subjected to machine-assisted slow COR for ≈120 minutes before transplantation. A cohort of 178 patients transplanted during the same period with similar clinical characteristics were used for comparison of key outcomes. RESULTS: All livers were perfused in accordance to the COR protocol without incidences and transplanted successfully. Early allograft dysfunction was observed in 2 (11.1%) cases after COR. Liver elasticity measurements indicated normal healthy liver parenchyma at the last follow-up. Graft survival demonstrated excellent outcomes after COR. The 1-, 3-, and 5-year patient survival rates were 100%, 100%, and 93.8% compared with 84.5%, 82.0%, and 75.8% in the control group (P = 0.12). CONCLUSIONS: The present study demonstrates excellent clinical outcomes after COR before liver transplantation. Comparison with a control cohort shows superiority of graft survival. Further evidence is needed to assess this promising method to improve organ preservation, finally.

Women in surgery: a web-based survey on career strategies and career satisfaction.

Women represent the majority of medical students in several countries. In any surgical specialty and above all in surgical leadership positions, women still remain disproportionally underrepresented. The objective of this study was to investigate female surgeons' career advancement and satisfaction with training. A standardized questionnaire was devised and sent out via the web-based survey tool SurveyMonkey® to female surgeons in the German federal state of North Rhine-Westphalia. A total of 125 completed questionnaires were analyzed (response rate 40.8%). Female surgeons are at least largely (76%) satisfied with their surgical training. Increased time (>5 h/week) as the principal surgeon in the operating room significantly stimulates the satisfaction with the surgical training (86% vs. 68%, p = 0.0384). At the participants' current workplace, the heads of departments are predominantly male surgeons (91%). Respondents not satisfied with their surgical training prefer a female head of department more frequently (24% vs. 2%, p = 0.0085). The majority of the respondents themselves aspire to become a consultant surgeon (56%), while only 12% intend to become a head of a department. Female surgeons aiming at leadership positions work overtime (≥50 h/week) significantly more frequently (81% vs. 57%, p = 0.0041). Favoritism of male colleagues is perceived by 34%. Respondents who do not perceive any preferential treatment are significantly more satisfied with their surgical training (88% vs. 57%, p = 0.0004). In conclusion, female surgeons seem positive about their career choice, once in the surgical profession, and aptly fill upcoming positions. Women interested in surgery are likely to pursue a surgical career despite the alleged workload, demonstrating the importance of professional self-fulfillment among female surgeons.

Long-term outcome of third, fourth and fifth kidney transplantation: technical aspects and immunological challenges.

BACKGROUND: The number of patients on waiting lists for repeated kidney transplantation has increased. However, retransplanted patients have a greater surgical and immunological risk than first-time kidney recipients. METHODS: We retrospectively analysed all kidney recipients that underwent third, fourth or fifth kidney transplantation (Group 3+) at the University Hospital Essen, Essen, Germany from October 1973 to January 2017. A historical cohort of recipients retransplanted with a second kidney (Group 2) served as the control. Donor and recipient demographic data, cold ischaemia time (CIT), warm ischaemia time, overall operation time and methods, transplantectomy of previous kidney grafts, incidence of surgical and immunological complications as well as patient- and death-censored survival were analysed. RESULTS: We identified 108 recipients transplanted with the third, fourth or fifth renal allograft. Patients with more than one transplantation had significantly higher surgical risk due to atherosclerosis (P = 0.002) and higher immunological risk due to higher panel reactive antibody levels preoperatively (current panel reactive antibody P = 0.004; highest panel reactive antibody value P = 0.0001). Group 3+ patients had more often undergone previous transplant nephrectomy (P = 0.0001). There was a significant difference in CIT (P = 0.009), overall operative time (P = 0.0001) and post-transplantation thrombotic events (P = 0.02). We could not demonstrate any differences in graft and patient survival. CONCLUSION: Third, fourth and fifth transplant recipients are a high-risk patient cohort. Our results suggest that patient survival after more than three renal transplantations is similar to that of second graft recipients. This supports the concept of repeated kidney retransplantations.

Analysis of Data from the Oxygen Persufflation in Liver Transplantation (OPAL) Study to Determine the Role of Factors Affecting the Hepatic Microcirculation and Early Allograft Dysfunction.

BACKGROUND Adequate microcirculatory perfusion is essential for the provision of oxygen to the liver following transplantation. Data from the Oxygen Persufflation in Liver Transplantation (OPAL) study (ISRCTN00167887) were analyzed from liver transplants performed at a single center to determine the role of factors affecting the hepatic microcirculation and early allograft dysfunction (EAD). MATERIAL AND METHODS Retrospective data from 116 patients from the Oxygen Persufflation as Adjunction in Liver Transplantation (OPAL) study who underwent liver transplantation at a single center were analyzed. Oxygen saturation of hemoglobin (SO2), relative capillary hemoglobin concentration (rHb), relative tissue blood flow (rBF) using laser Doppler flow measurements, and the Oxygen-to-See (O2C) spectrometry were measured and with post-transplant allograft function were analyzed using univariate and multivariate logistic regression statistics. RESULTS Livers donors had a median donor risk index of 1.8. Most liver transplant recipients were men (60.3%), with a median age of 54 years (IQR, 23-68 years). Mean post-transplant 3-month survival was 90.5%. The EAD rate was 22.4%, the median SO2 was 78% (IQR, 29.5-95.8%), the median rHb was 55.6 AU (IQR, 16.8-74.8 AU), and the median rBF was 110.1 AU (IQR, 35.8-406.8 AU). Multivariate logistic regression analysis showed that tissue SO2 (p=0.01), body mass index (BMI) of the transplant recipient (p=0.002), serum alanine transaminase (ALT) of the donor (p=0.02), and portal blood flow (p=0.01) were predictive factors for EAD. CONCLUSIONS Non-invasive investigations of the liver microcirculation and hemoglobin oxygenation were shown to be predictive factors for EAD following liver transplantation.

Ileostomy for steroid-resistant acute graft-versus-host disease of the gastrointestinal tract.

Steroid-resistant acute graft-versus-host disease (GVHD) of the gastrointestinal tract associates with important morbidity and mortality. While high-dose steroids are the established first-line therapy in GVHD, no second-line therapy is generally accepted. In this analysis of 65 consecutive patients with severe, steroid-resistant, intestinal GVHD (92% stage 4), additional ileostomy surgery significantly reduced overall mortality (hazard ratio 0.54; 95% confidence interval, 0.36-0.81; p = 0.003) compared to conventional GVHD therapy. Median overall survival was 16 months in the ileostomy cohort compared to 4 months in the conventional therapy cohort. In the ileostomy cohort, both infectious- and GVHD-associated mortality were reduced (40% versus 77%). Significantly declined fecal volumes (p = 0.001) after surgery provide evidence of intestinal adaptation following ileostomy. Correlative studies indicated ileostomy-induced immune-modulation with a > 50% decrease of activated T cells (p = 0.04) and an increase in regulatory T cells. The observed alterations of the patients' gut microbiota may also contribute to ileostomy's therapeutic effect. These data show that ileostomy induced significant clinical responses in patients with steroid-resistant GVHD along with a reduction of pro-inflammatory immune cells and changes of the intestinal microbiota. Ileostomy is a treatment option for steroid-resistant acute GVHD of the gastrointestinal tract that needs further validation in a prospective clinical trial.

Risk Factors for High Mortality on the Liver Transplant Waiting List in Times of Organ Shortage: A Single-Center Analysis.

BACKGROUND Germany has the highest rate of patients dying or becoming unfit for transplant while waitlisted within the Eurotransplant region. Therefore, the aim of the current study was to analyze mortality as well as risk factors for mortality of candidates listed for liver transplantation at our center. MATERIAL AND METHODS Between 01/2011 and 12/2013, 481 adult patients were listed for primary liver transplantation (LT) at a single German center. Clinical and laboratory parameters were prospectively collected and retrospectively analyzed by univariable and multivariable logistic regression and Cox proportional hazards. RESULTS The mean model for end-stage liver disease (MELD) score of all liver transplant waitlist registrants (52.4 years, 60.1% male) was 16.9 (±10.2) at time of listing, with 10% of the listed patients having a MELD score of >32. After waitlisting, 133 (27.7%) candidates died within the follow-up period. Three-month-survival after listing for transplantation was 89% for patients ultimately receiving LT vs. 71.2% that did not receive LT (p<0.001). Multivariable analysis identified clinical parameters such as ICU treatment, preceding abdominal surgery, variceal bleeding, and ascites, as well as hydropic decompensation, as independent risk factors for waitlist mortality. CONCLUSIONS Consideration of independent risk factors of mortality within the MELD-based allocation system potentially improves assessment of individual urgency and might improve utilization of available organs.

Evaluation of hemostasis in patients with end-stage renal disease.

An increased bleeding risk is reported for patients with end-stage renal disease. This study aims to analyze, whether bleeding risk can be assessed by global tests of hemostasis. Standard laboratory tests and an extended evaluation of hemostasis by rotational thromboelastometry, platelet function analyzer (PFA) and multiple electrode aggregometry as well as thrombin generation assays and measurement of fibrinolytic potential were performed in 20 patients on hemodialysis, 10 patients on peritoneal dialysis, 10 patients with chronic kidney disease stage G5 (CKD5) and in 10 healthy controls (HC). Hemoglobin was significantly lower in patients with end-stage renal disease versus HC (each p<0.01). Patients on peritoneal dialysis showed increased fibrinogen levels compared to HC (p<0.01), which were also reflected by FIBTEM results (each p<0.05). 41% of hemodialysis patients and 44% of CKD5 patients presented with prolonged PFA-ADP-test (p<0.05), while no patient on peritoneal dialysis and no HC offered this modification. Thrombin generating potential was significantly lower in patients on hemodialysis, while clot lysis time revealed a hypofibrinolytic state in patients on hemo- and peritoneal dialysis compared to HC (p<0.001). In conclusion, patients with end-stage renal disease have complex hemostatic changes with both hyper- and hypocoagulable features, which are dependent on use and type of dialysis. Hypercoagulable features include elevated fibrinogen levels and a hypofibrinolytic state, whereas hypocoagulable features include decreased thrombin generating capacity and platelet dysfunction. Our results may contribute to a more rational approach to hemostatic management in these patients.

Liver Transplantation From Donors With a History of Malignancy: A Single-Center Experience.

BACKGROUND: The demand for transplantable organs exceeds donor organ supply. Transplantation of organs from donors with a history of malignancy remains controversial and the transmission of cancer in liver transplant recipients has not been sufficiently examined. METHODS: From 2002 until 2017, 83 livers from donors with a history of malignancy were transplanted at the University Hospital Essen, Germany. Donor and recipient data, type of malignancy, tumor-free interval at organ procurement, and follow-up data were analyzed. RESULTS: Nine different tumor sites (central nervous system [n = 27], genitourinary [n = 24], breast [n = 10], skin [n = 8], colorectal [n = 5], lung [n = 3], hemato-oncological [n = 3], thyroid [n = 2], and larynx [n = 1]) were detected in 83 donors. The majority (58%) of donors had tumor-free intervals of less than 5 years versus 19% of 6 to 10 years versus 23% over 10 years. The risk of tumor transmission from donors was assessed as low in 44 (53%), intermediate in 28 (34%), and high in 11 (13%) cases. During median follow-up of 19.9 (0-155) months, none of the recipients developed donor-transmitted malignancy. CONCLUSIONS: Liver transplantation with organs from donors with a medical history of malignancy is feasible, and the risk of donor-transmitted malignancy appears to be low in this single-center analysis. A careful selection of donors remains mandatory and can expand the donor pool.

Transplantation of Renal Allografts From Organ Donors Reactive for HCV Antibodies to HCV-Negative Recipients: Safety and Clinical Outcome.

INTRODUCTION: Because of the shortage of available organs for renal transplantation, strategies enabling the safe use of organs from donors with potential chronic infections such as hepatitis C are necessary. The aim of this study was to analyze the outcome of renal transplant donation from hepatitis C virus (HCV)-positive donors. METHODS: Between September 2002 and May 2007, 51 kidneys (34 donors) reactive for HCV antibodies were further evaluated. Six kidneys (5 donors) were transplanted to 6 recipients with known chronic HCV infection. The remaining 29 donors underwent extended virological testing. Nine donors were HCV RNA positive and thus not suitable for HCV-negative patients. Twenty donors (21 kidneys) did not have detectable HCV RNA copies and were transplanted into 21 HCV-negative recipients. Clinical outcomes focusing on safety, allograft function, and de novo HCV infection in the recipient were collected. RESULTS: There were no de novo HCV infections detected in recipients who were HCV negative before transplantation. The extended virological donor screening did not have an impact on median cold ischemia time. Five-year graft survival was 75%. DISCUSSION: Organs from anti-HCV-reactive, nonviremic donors can be transplanted safely to HCV-negative recipients.

Hepatic artery and biliary complications in liver transplant recipients with radioembolization bridging treatment for hepatocellular carcinoma.

BACKGROUND: Locoregional bridging treatments are commonly applied in patients with hepatocellular carcinoma (HCC) prior to liver transplantation to prevent tumor progression during waiting time. It remains unknown whether pre-transplant radioembolization treatment may increase the prevalence of hepatic artery and biliary complications post-transplant. METHODS: We performed a retrospective review of 173 consecutive patients with HCC who underwent liver transplantation at our transplant center between January 2007 and December 2016. RESULTS: Radioembolization bridging treatment was applied in 42 patients while 131 patients received other or no forms of bridging treatment. The overall prevalence of intra-operative and early post-operative hepatic artery complications was 9.5% in the radioembolization group and 9.2% in the control group (P = 1.000). Biliary complications were significantly less frequent in the radioembolization group (4.8% vs 17.6%, P = .0442). In multivariable analysis, radioembolization was not significantly associated with an increased risk of arterial complications. Considering biliary complications, radioembolization bridging treatment was the only factor significantly associated with decreased odds (OR 0.187 (0.039, 0.892), P = .036). CONCLUSIONS: Radioembolization is not associated with higher odds of hepatic artery complications following liver transplantation. There may even be a protective effect regarding biliary complications. Radioembolization as a bridge to transplantation may effectively be applied without compromising successful liver transplantation.

Long-Term Outcome After Liver Transplantation for Hepatocellular Carcinoma Following Yttrium-90 Radioembolization Bridging Treatment.

BACKGROUND Bridging treatments are employed in liver transplant waitlist patients with hepatocellular carcinoma (HCC) because of the risk of tumor progression during the waiting time. Radioembolization is mostly employed in the control of large or multifocal HCCs when other locoregional treatment modalities cannot be applied because of the number or size of lesions. The purpose of this study was to evaluate our experience with the use of radioembolization as a bridge to transplantation and its effect on tumor recurrence and survival after liver transplantation. MATERIAL AND METHODS A retrospective review of 40 consecutive patients with HCC who underwent liver transplantation after radioembolization bridging treatment between January 2007 and December 2015 at the University Hospital Essen, Germany, was performed. Patients' characteristics, alpha-fetoprotein (AFP) levels, pathologic tumor response, tumor recurrence rate, and survival rates were examined through chart review. RESULTS Histopathological examination of the explanted liver specimen revealed complete tumor necrosis in 17 specimens, partial necrosis in 18 specimens, and no significant necrosis in five specimens. Median overall survival was 46 months. Nine patients developed recurrent HCC. Median time from liver transplantation to diagnosis of tumor recurrence was 15 months. There was a trend towards a lower risk of tumor recurrence for patients with complete necrosis on explant specimens. Patients with tumor recurrence demonstrated statistically significantly higher pre- and post-treatment AFP levels (p=0.0234 and p=0.0236) and statistically significantly more frequently microvascular invasion (p=0.0163). CONCLUSIONS Histopathological assessment of explanted livers revealed at least partial necrosis in 87.5% of patients. Patients with successful bridging treatment, i.e. complete necrosis of explant specimens, demonstrate a trend towards a lower risk of tumor recurrence.

The postoperative Model for End stage Liver Disease score as a predictor of short-term outcome after transplantation of extended criteria donor livers.

BACKGROUND: Recently, the postoperative Model for End stage Liver Disease score (POPMELD) was suggested as a definition of postoperative graft dysfunction and a predictor of outcome after liver transplantation (LT). AIM: The aim of the present study was to validate this concept in the context of extended criteria donor (ECD) organs. PATIENTS AND METHODS: Single-center prospectively collected data (OPAL study/01/11-12/13) of 116 ECD LTs were utilized. For each recipient, the Model for End stage Liver Disease (MELD) score was calculated for 7 postoperative days (PODs). The ability of international normalized ratio, bilirubin, aspartate aminotransferase, Donor Risk Index, a recent definition of early allograft dysfunction, and the POPMELD was compared to predict 90-day graft loss. Predictive abilities were compared by receiver operating characteristic curves, sensitivity and specificity, and positive and negative predictive values. RESULTS: The median Donor Risk Index was 1.8. In all, 60.3% of recipients were men [median age of 54 (23-68) years]. The median POD1-7 peak-aspartate aminotransferase value was 1052 (194-17 577) U/l. The rate of early allograft dysfunction was 22.4%. The 90-day graft survival was 89.7%. Out of possible predictors of the 90-day graft loss MELD on POD5 was the best predictor of outcome (area under the curve=0.84). A MELD score of 16 or more on POD5 predicted the 90-day graft loss with a specificity of 80.8%, a sensitivity of 81.8%, and a positive and negative predictive value of 31 and 97.7%. CONCLUSION: A MELD score of 16 or more on POD5 is an excellent predictor of outcome in ECD donor LT. Routine evaluation of POPMELD scores might support clinical decision-making and should be reported routinely in clinical trials.

Reconditioning by end-ischemic hypothermic in-house machine perfusion: A promising strategy to improve outcome in expanded criteria donors kidney transplantation.

This clinical study evaluates end-ischemic hypothermic machine perfusion (eHMP) in expanded criteria donors (ECD) kidneys. eHMP was initiated upon arrival of the kidney in our center and continued until transplantation. Between 11/2011 and 8/2014 eHMP was performed in 66 ECD kidneys for 369 (98-912) minutes after 863 (364-1567) minutes of cold storage (CS). In 49 of 66 cases, the contralateral kidney from the same donor was preserved by static CS only and accepted by another Eurotransplant (ET) center. Five (10.2%) of these kidneys were ultimately judged as "not transplantable" by the accepting center and discarded. After exclusion of early unrelated graft losses, 43 kidney pairs from the same donor were eligible for direct comparison of eHMP vs CS only: primary non-function and delayed graft function (DGF) were 0% vs 9.3% (P=.04) and 11.6% vs 20.9% (P=.24). There was no statistically significant difference in 1-year graft survival (eHMP vs CS only: 97.7% vs 88.4%, P=.089). In a multivariate analysis, eHMP was an independent factor for prevention of DGF (OR: 0.28, P=.041). Development of DGF was the strongest risk factor for 1-year graft failure (Renal resistance: 38.2, P<.001). In summary, eHMP is a promising reconditioning technique to improve the quality and acceptance rate of suboptimal grafts.